Melanin seeking compounds as melanoma localizing or therapeutic agents have a major limitation in that the normal melanin containing structures are frequently encountered clinically as background in the location of the tumor. This limits the usefulness of these compounds for therapy and diagnosis as they are bound to pre-formed melanin in both tumor and normal tissue. Our clinical experience with an iodine-123 (I-123) labeled quinoline derivative was unsuccessful in localizing choroidal melanoma. This was in part due to the high background uptake of the melanin containing structures of the eye as well as the high uptake by the brain. However, the need in clinical ophthalmology for the melanoma localizing agent is now greater because of the increased use of radiotherapy wherein no tissue diagnosis is obtained. The difficulties in differentiating choroidal nevi from small malignant melanoma continues to plague ophthalmology. Small animal data show that the false melanin precursor thiouracil (TU) has a high concentration in Harding-Passey melanoma (approximately 10% dose/g), while retention in other tissues is approximately 100 times less. The uptake by other pigmented tissues such as the choroid of the eye is low, as incorporation of TU occurs only as melanin is being formed. The purpose of this study is to investigate the therapeutic and diagnostic potential of labeled thiouracil in humans. We have successfully synthesized I-125-TU, and found that it was incorporated into the biosynthetic pathway of melanin to the same degree as TU itself. Uptake studies of I-125-TU in our murine melanoma were so encouraging that extension to clinical trials now seems appropriate. It is anticipated that I-123-TU will be useful in the diagnosis of human melanoma. Therapy studies with sulfur-35-TU (S-35) in our Harding-Passey model demonstrated that tumor growth could be suppressed for 2 to 3 weeks. Further animal studies are planned before clinical trials in humans. However our preliminary data indicates that S-35-TU, or perhaps more likely I-131-TU, will find a useful place in the radiotherapy of human melanoma.